Stimulation of the Ileal Brake Hormones by an Orally Delivered Natural Product (Aphoeline I) to the Terminal Ileum of Healthy Volunteers

Abstract Amylase is elevated in the foregut and has been used to confirm anastomotic integrity after pancreatic surgery. The physiological activity of pancreatic enzymes in the ileum has been studied in healthy volunteers but not quantitated with the simple and readily available amylase measurements employed with serum tests. We aim to quantitate the levels of amylase in the terminal ileum. This was a prospective, non-randomised, non-blinded, consecutive cohort study conducted at the Royal Brisbane and Women’s Hospital. Consecutive patients undergoing routine surgery with an ileostomy were invited to participate in the study. Ileostomy effluent was collected and analysed daily for the first 5 post-operative days. This validation cohort included 8 males and 3 females, with a mean age of 49 years. Median daily amylase levels ranged from 4470 U/L to 23,000 U/L, with no specimens falling within the laboratory serum reference range of 40 to 130 U/L. Two specimens were not available on day one post-operative due to complete ileus. The sample size of 11 patients is small but was considered sufficient given that 55 effluent specimens were anticipated for analysis. Amylase levels remain highly elevated as the enzyme transits through the length of the small intestine and measured in the terminal ileum, and can be readily quantitated by the existing testing methodology routinely available.

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Dual effects of cisapride on gastric emptying and antropyloroduodenal motility

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1993.264.2.g195 ◽

1993 ◽

Vol 264 (2) ◽

pp. G195-G201 ◽

Cited By ~ 5

Author(s):

R. Fraser ◽

M. Horowitz ◽

A. Maddox ◽

J. Dent

Keyword(s):

Gastric Emptying ◽

Healthy Volunteers ◽

Gastric Motility ◽

Normal Subjects ◽

Solid Component ◽

Pressure Waves ◽

Dual Effect ◽

Intravenous Saline ◽

Plausible Mechanism ◽

Stimulation Of

There is little information about the effects of cisapride on human antropyloroduodenal motility, despite its documented efficacy for increasing the rate of gastric emptying in patients with gastroparesis. Cisapride has been reported to have little effect on gastric emptying in normal subjects. Antral, pyloric, and duodenal pressures were recorded simultaneously with gastric emptying in 20 healthy volunteers. Thirty minutes after the solid component of the meal had started to empty from the stomach, each subject received either 10 mg cisapride i.v. (11 subjects) or intravenous saline (9 subjects). Intravenous saline had no effect on either motility or gastric emptying. In contrast, cisapride administration was associated with a dual effect on motility, with initial suppression of antral pressure waves (P < 0.05) followed by stimulation of associated antropyloroduodenal pressure waves (P < 0.01). Gastric emptying slowed in the first 30 min after cisapride (P < 0.05), and this was followed by more rapid gastric emptying (P < 0.01). The amount of the meal emptied in the 60 min after cisapride correlated with the number of associated antroduodenal pressure waves (r = 0.75, P < 0.001) but not with the number of antral waves (r = 0.42, NS). These results indicate that cisapride in a dose of 10 mg i.v. has dual effects on gastric emptying and gastric motility. The stimulation of associated antral pressure waves is a plausible mechanism for the efficacy of cisapride in the treatment of gastroparesis.

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VIP is involved in peripheral CRF-induced stimulation of propulsive colonic motor function and diarrhea in male rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00308.2017 ◽

2018 ◽

Vol 314 (5) ◽

pp. G610-G622 ◽

Cited By ~ 2

Author(s):

Seiichi Yakabi ◽

Lixin Wang ◽

Hiroshi Karasawa ◽

Pu-Qing Yuan ◽

Kazuhiko Koike ◽

...

Keyword(s):

Vasoactive Intestinal Peptide ◽

Motor Function ◽

Terminal Ileum ◽

Proximal Colon ◽

Corticotropin Releasing Factor ◽

Submucosal Plexus ◽

Myenteric Neurons ◽

Colonic Motor ◽

Fos Expression ◽

Stimulation Of

We investigated whether vasoactive intestinal peptide (VIP) and/or prostaglandins contribute to peripheral corticotropin-releasing factor (CRF)-induced CRF1 receptor-mediated stimulation of colonic motor function and diarrhea in rats. The VIP antagonist, [4Cl-D-Phe6, Leu17]VIP injected intraperitoneally completely prevented CRF (10 µg/kg ip)-induced fecal output and diarrhea occurring within the first hour after injection, whereas pretreatment with the prostaglandins synthesis inhibitor, indomethacin, had no effect. In submucosal plexus neurons, CRF induced significant c-Fos expression most prominently in the terminal ileum compared with duodenum and jejunum, whereas no c-Fos was observed in the proximal colon. c-Fos expression in ileal submucosa was colocalized in 93.4% of VIP-positive neurons and 31.1% of non-VIP-labeled neurons. CRF1 receptor immunoreactivity was found on the VIP neurons. In myenteric neurons, CRF induced only a few c-Fos-positive neurons in the ileum and a robust expression in the proximal colon (17.5 ± 2.4 vs. 0.4 ± 0.3 cells/ganglion in vehicle). The VIP antagonist prevented intraperitoneal CRF-induced c-Fos induction in the ileal submucosal plexus and proximal colon myenteric plexus. At 60 min after injection, CRF decreased VIP levels in the terminal ileum compared with saline (0.8 ± 0.3 vs. 2.5 ± 0.7 ng/g), whereas VIP mRNA level detected by qPCR was not changed. These data indicate that intraperitoneal CRF activates intestinal submucosal VIP neurons most prominently in the ileum and myenteric neurons in the colon. It also implicates VIP signaling as part of underlying mechanisms driving the acute colonic secretomotor response to a peripheral injection of CRF, whereas prostaglandins do not play a role. NEW & NOTEWORTHY Corticotropin-releasing factor (CRF) in the gut plays a physiological role in the stimulation of lower gut secretomotor function induced by stress. We showed that vasoactive intestinal peptide (VIP)-immunoreactive neurons in the ileal submucosal plexus expressed CRF1 receptor and were prominently activated by CRF, unlike colonic submucosal neurons. VIP antagonist abrogated CRF-induced ileal submucosal and colonic myenteric activation along with functional responses (defecation and diarrhea). These data point to VIP signaling in ileum and colon as downstream effectors of CRF.

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Peptide histidine valine-42 stimulates gastric acid secretion in man

Bioscience Reports ◽

10.1007/bf01114690 ◽

1989 ◽

Vol 9 (3) ◽

pp. 369-374 ◽

Cited By ~ 2

Author(s):

G. C. Nikou ◽

Y. Yiangou ◽

B. J. Chrysanthou ◽

J. Domin ◽

S. R. Bloom

Keyword(s):

Gastric Secretion ◽

Acid Secretion ◽

Healthy Volunteers ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Local Control ◽

Significant Stimulation ◽

New Finding ◽

Stimulation Of

The effect of peptide histidine valine-42 (PHV-42) on gastric acid secretion was studied in man. PHV-42 was infused into 5 healthy volunteers at a dose of 10 pmol/kg/min. This dose caused a significant stimulation of basal gastric acid and potassium output. there were no significant changes in circulating gastrin throughout the infusion. In 2 subjects with a background of submaximal pentagastrin stimulation, PHV-42 infusion at the same dose did not alter acid secretion in either subject. The previous observation that PHV-42 is found particularly in the stomach and the new finding that it stimulates basal gastric secretion suggest the possibility that PHV-42 could have a role in local control of acid secretion.

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Ileal tone in humans: effects of locoregional distensions and eating

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1994.267.4.g569 ◽

1994 ◽

Vol 267 (4) ◽

pp. G569-G574 ◽

Cited By ~ 6

Author(s):

B. Coffin ◽

M. Lemann ◽

B. Flourie ◽

L. Picon ◽

J. C. Rambaud ◽

...

Keyword(s):

Healthy Volunteers ◽

Linear Relationship ◽

Terminal Ileum ◽

Second Phase ◽

Tonic Activity ◽

Phasic Activity ◽

Tonic Response

Using an electronic barostat in the human terminal ileum, we studied ileal tone in response to various stimuli in 10 healthy volunteers. Phasic activity was also measured by manometry. Graded orad (ileal) and caudad (cecal) balloon distensions did not produce any significant changes in ileal tone at all levels tested, even when a sensation of discomfort was felt. A linear relationship between pressure and volume was observed during in situ isobaric ileal distensions. Meal induced a biphasic tonic response with a brief (20 min) and immediate decrease in intrabag volume (64 +/- 7% of preprandial value, P < 0.05), followed by a prolonged increase in intrabag volume (158 +/- 10% of preprandial value, P < 0.05). A significant correlation was found between volume variations and phasic activities during the first phase (r = 0.88, P < 0.05), whereas no correlation was found during the second phase (r = 0.55, NS). The administration of glucagon induced a significant increase in intrabag volume from 45 +/- 5 to 70 +/- 8 ml (P < 0.05). We conclude that 1) regional distensions do not influence ileal tone and phasic motility, 2) the ileum does not show accommodation to distensions, and 3) meal produces an immediate increase in phasic and tonic activity followed by a prolonged relaxation.

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The Effects of Heparinase 1 and Protamine on Platelet Reactivity

Anesthesiology ◽

10.1097/00000542-199706000-00021 ◽

1997 ◽

Vol 86 (6) ◽

pp. 1382-1386 ◽

Cited By ~ 58

Author(s):

Tameshwar Ammar ◽

Cherie F. Fisher

Keyword(s):

Healthy Volunteers ◽

Receptor Agonist ◽

Platelet Reactivity ◽

Institutional Review Board ◽

Thrombin Receptor ◽

Agonist Peptide ◽

Institutional Review ◽

Heparin Anticoagulation ◽

Baseline Values ◽

Stimulation Of

Background Protamine is currently the most widely used drug for the reversal of heparin anticoagulation. Heparinase 1 (heparinase) is being evaluated as a possible alternative to protamine for the reversal of heparin anticoagulation. The authors evaluated the effects of equivalent doses of heparinase and protamine on platelet reactivity by measuring agonist-induced P-selectin expression. Methods After Institutional Review Board (IRB) approval, informed consent was obtained from 12 healthy volunteers and 8 patients undergoing surgery requiring cardiopulmonary bypass (CPB). Twenty-four ml of blood was obtained from each volunteer; 10 ml of blood was obtained from each patient before the CPB, and another 10 ml was obtained after CPB. Heparin was neutralized using heparinase or protamine. Platelet reactivity was assessed by measuring the expression of P-selectin after stimulation of platelets with increasing concentrations of a thrombin receptor agonist peptide (TRAP). Data were analyzed using analysis of variance. P < 0.05 was considered significant. Results For the healthy volunteers, the activated coagulation times (ACTs) of the heparinized samples returned to baseline values with heparinase (12.5 U/ml) or protamine (32.5 microg/ml). For the 8 patients, the ACTs returned to baseline with heparinase (20 U/ml) or protamine (50 microg/ml). The authors found no difference in the expression of P-selectin in samples neutralized with heparinase, but samples neutralized with protamine showed a significant decrease in the expression of P-selectin when compared with heparinized samples. Conclusions At dosages that reverse the anticoagulant effects of heparin, heparinase has minimal effects on platelets, whereas platelet reactivity was markedly inhibited by protamine.

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Clinical Study of Objective Pulse Diagnosis

The American Journal of Chinese Medicine ◽

10.1142/s0192415x86000296 ◽

1986 ◽

Vol 14 (03n04) ◽

pp. 179-183 ◽

Cited By ~ 6

Author(s):

Sook Hyang Yoon ◽

Yoshihisa Koga ◽

Isao Matsumoto ◽

Etsutaro Ikezono

Keyword(s):

Clinical Study ◽

Healthy Volunteers ◽

Pain Threshold ◽

Acupuncture Analgesia ◽

Pulse Diagnosis ◽

Element Theory ◽

Stimulation Of

The recording of the objective pulse diagnosis was performed and that meridian points were selected from this recording. The proper meridian points (five element points) according to the five element theory and the improper points (non-five element points) were stimulated. Pain threshold was elevated by the stimulation of five element points and not raised by non-five element points in a patient who had nasal ploypectomy under acupuncture analgesia and also in 6 of 9 healthy volunteers. Naloxone reversal of elevated pain threshold was also observed in volunteers.

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